Effects of antisense oligodeoxynucleotides on peptide release from hypothalamoneurohypophysial explants

M Ludwig, M Morris, C D Sladek

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Rapid effects of antisense oligodeoxynucleotides (AODNs) on the function of the neurohypophysial system have been reported previously. The present studies were designed to determine the effects of vasopressin (VP) and oxytocin (OT) AODNs on osmotically or potassium-stimulated VP and OT release from perifused hypothalamoneurohypophysial (HNS) explants. The AODNs were 18-mer phosphorothioate forms targeted toward the translation initiation sites of either VP or OT mRNA, or a mixed base sequence (4 microM). The explants were exposed to a ramp increase in NaCl (either 20 or 30 mosmol/6 h) or to 25 mM KCl. VP and OT release was measured by radioimmunoassay in sequential 20-min fractions of the perifusate. There was a peptide-specific inhibition by the AODNs of osmotically stimulated VP and OT release. VP AODN inhibited VP, but not OT release, and vice vorsa. However, the AODNs had no effect on potassium-stimulated peptide release, demonstrating that depolarization-secretion coupling was still intact. Furthermore, there were no significant differences in VP and OT mRNA and peptide content after antisense treatment. Thus these observations indicate that acute exposure to peptide AODNs interrupts osmotically stimulated VP and OT release in a peptide-specific manner.

Original languageEnglish
Pages (from-to)R1441-6
JournalAmerican Journal of Physiology - Regulatory, Integrative and Comparative Physiology
Volume272
Issue number5 Pt 2
Publication statusPublished - May 1997

Keywords / Materials (for Non-textual outputs)

  • Animals
  • Hypothalamo-Hypophyseal System
  • Male
  • Oligonucleotides, Antisense
  • Oxytocin
  • Potassium
  • RNA, Messenger
  • Rats
  • Rats, Sprague-Dawley
  • Vasopressins
  • Water-Electrolyte Balance

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